LFT tests is also called hepatic panel. Noninvasive methods for screening of liver dysfunction. They reflect the synthetic function and evidence of liver damage. These tests provide insights into several aspects of liver health, Its ability to synthesize enzymes and protein. Its ability to process bilirubin and secrete bile. And the extent of liver damage.

1. LIVER FUNCTION
TEST
Asha Prerna Tigga

2. LFT
◦ LFT tests is also called hepatic panel.
◦ Noninvasive methods for screening of liver dysfunction.
◦ They reflect the synthetic function and evidence of liver damage.
◦ These tests provide insights into several aspects of liver health,
Its ability to synthesize enzymes and protein.
Its ability to process bilirubin and secrete bile.
And the extent of liver damage.

3. LFT
◦ Abnormal LFT results do not always indicate liver disease. Some
abnormalities are transient; or they may result from different, non-
hepatic causes.
◦ Abnormal LFTs are found in about 8% of population- about 30% of
them are transient.

4. Anatomy of liver
◦ The liver, located in the right upper quadrant of
the body and below the diaphragm, is
responsible for several functions.
◦ It is a soft, reddish brown, triangular organ
with four lobes.
◦ A human liver weighs between 1.44 kg to 1.66
kg.

5. Functions of the Liver
◦ Synthetic Function
◦ Plasma proteins (albumin, globulins), cholesterol, triglycerides and
lipoproteins
◦ Detoxification and excretion
◦ Ammonia to urea (urea cycle), bilirubin, cholesterol, drug metabolites
◦ Storage Function
◦ Vitamins A, D, E, K and B12
◦ Secretory function
◦ Bile production: Helps in digestion
◦Bilirubin: conjugation and secretion of bilirubin.

6. Functions of the Liver
◦ Vascular function
◦ Blood filtration: breakdown of old RBCs
◦ Blood reservoir
◦ Metabolic function
◦ Blood clotting: synthesis of Prothrombin and fibrinogen and
other factors.
◦ Fat and protein metabolism.

7. Epidemiology
• Elevated liver chemistries are found in approximately 8% of the general
population.
• These elevations may be transient in patients without symptoms with
up to 30% elevations resolving after 3 weeks.
• Thus, care should be taken when interpreting these results to avoid
unnecessary testing.

8. USE of LFT Test
(1)Detect the presence of liver disease
(2)Distinguish among different types of
liver disorders
(3)Gauge the extent of known liver
damage
(4)Follow the response to treatment.

9. LIMITATIONS
◦ Lack sensitivity: The LFT may be normal in certain liver diseases like cirrhosis,
non cirrhotic portal fibrosis, congenital hepatic fibrosis, etc.
◦ Lack specificity: They lack specificity and are not specific for any particular
disease. Serum albumin may be decreased in chronic disease and also in
nephrotic syndrome. Aminotransferases may be raised in cardiac diseases and
hepatic diseases.
◦ Except for serum bile acids the LFT are not specific for liver diseases and all the
parameters may be elevated for pathological processes outside the liver.

10. Common causes of liver dysfunction
◦ Hepatocellular disease
◦ Steatosis (Alcohol or weight related)
◦ Steatohepatitis
◦ Cholestasis (obstruction of bile flow)
◦ Cirrhosis
◦ Viral Hepatitis
◦ Jaundice
◦ Liver cancer
◦ Metabolic diseases (Wilson’s diease)
◦Genetic Disorders
◦ Hemochromatosis (iron storage)

11. LFT is Broadly classified as:
1.Tests to detect hepatic injury:
• Mild or severe; acute or chronic
• Nature of liver injury (hepatocellular or cholestasis)
2.Tests to assess hepatic function
Group I: Markers of liver dysfunction
▫ Serum bilirubin: total and conjugated
▫ Urine: bile salts and urobilinogen
▫ Total protein, serum albumin and albumin/globulin ratio
▫ Prothrombin Time

12. LFT is Broadly classified as:
2.Tests to assess hepatic function
Group II: Markers of hepatocellular injury
▫ Alanine aminotransferase (ALT)
▫ Aspartate aminotransferase (AST)
Group III: Markers of cholestasis
▫ Alkaline phosphatase (ALP)
▫ Gamma-glutamyl transferase (GGT)

13. LFTs value
Serum Bilirubin total 0.3 – 1.2 mg/dl
Serum Bilirubin Direct < 0.2 mg/dl
Serum Bilirubin Indirect 0.2 – 0.8 mg/dl
Serum AST 5 – 40 IU/L
Serum ALT < 19 IU/L
Serum Alkaline phosphate 30 – 120 IU/L
Serum GGT < 38 IU/L
Serum Total protein 6.4 – 8.3 g/dl
Serum Albumin 3.8 – 5.4 g/dl
Serum Globulin
A/G Ratio 1.5 – 5.4 g/dl

14. Bilirubin
 Bilirubin is the product of haemoglobin breakdown.
 Lipid-soluble, unconjugated bilirubin is conjugated in the liver, making it water-
soluble, and then excreted into bile.
 Majority of bilirubin circulates as unconjugated bilirubin and an elevated serum
conjugated bilirubin implies hepatocellular disease or biliary obstruction in most
settings.
 Normal serum bilirubin level varies from 0.3 to 1.2 mg/dL.
 The unconjugated bilirubin (free bilirubin) (indirect bilirubin) varies from 0.2–0.8
mg/dL and conjugated bilirubin (direct bilirubin) <0.2 mg/dL.

15. Bilirubin
 A rise in serum bilirubin above 1 mg/ dL is abnormal (latent jaundice); but
jaundice appears only if the level goes above 2 mg/dL.
 In case of raised bilirubin or clinical jaundice consider haemolysis
(production of unconjugated bilirubin), liver cell function (conjugation and
excretion of bilirubin) and biliary tree function (excretion of bile).

16. BILIRUBIN METABOLISM

19. Jaundice
Class of
Jaundice
Bilirubin Urine Stool Causes
Pre-hepatic
(hemolytic)
Unconjugated Normal Normal Abnormal red cells; antibodies;
drugs and toxins; thalessemia
Hemoglobinopathies, Gilbert’s
syndrome
Hepatic
(Hepatocellular)
Unconjugated/
Conjugated
Dark Normal Viral hepatitis, toxic hepatitis,
intrahepatic cholestasis
Post-hepatic
(Cholestasis)
Conjugated Dark Pale Extrahepatic cholestasis;
gallstones; tumors of the bile
duct, carcinoma of pancreas

20. ◦ Evaluation of abnormal liver function tests J K Limdi, G M Hyde, Postgrad Med J 2003;79:307–312

21. Urobilinogen (UBG) and bile salts
◦ Most UBG is metabolized in the large intestine but a fraction is excreted
in urine (less than 4 mg/day)
◦ Normally bile salts are NOT present in urine
◦ Obstruction in the biliary passages causes:
◦ Leakage of bile salts into circulation
◦ Excretion in urine

22. Serum Albumin
◦ Most abundant blood protein.
◦ Albumin synthesis is an important function of the liver. Approximately
10g is synthesized and secreted daily.
◦ Normal serum levels: 3.8 – 5.4 g/dL
◦ Synthesis depends on the extent of functioning liver cell mass
◦ Longer half-life: 20 days
◦ Function: maintain oncotic pressure in the blood, which stops fluid
leaking out of blood vessels.

23. Serum Albumin
◦ It indicates chronic liver damage
◦ Non Hepatic causes:
1. Low protein intake
2. Malabsorption
3. Nephrotic syndrome (Excessive Protein loss in urine)
4. Inflammatory response

24. Serum Globulin
◦ Normal serum levels: 2.5 – 3.5g/dL
 Immunoglobulins are produced by B lymphocytes.
 But alpha and beta globulins are synthesized mainly by hepatocytes.
◦ They constitute immunoglobulins (antibodies)
◦ High serum g-globulins are observed in chronic hepatitis and cirrhosis:
◦ IgG in autoimmune hepatitis
◦ IgA in alcoholic liver disease

25. Albumin to globulin (A/G) ratio
◦ Normal A/G ratio: 1.2/1 – 1.5/1
◦ Globulin levels increase in hypoalbuminemia as a
compensation

26. Prothrombin Time (PT)
◦ Normal Value: 10.9-12.5 sec
◦ Prothrombin: synthesized by the liver, a marker of liver
function
◦ Half-life: 6 hrs. (indicates the present function of the liver)
◦ PT is prolonged only when liver loses more than 80% of its
reserve capacity
◦ Vitamin K deficiency also causes prolonged PT
◦ Intake of vitamin K does not affect PT in liver disease

27. Aspartate aminotransferase (AST)
◦ Normal range: 5 – 40 U/L
◦ A marker of hepatocellular damage
◦ Non Hepatic causes
- Heart attack, muscular disease
◦ High serum levels are observed in:
◦ Chronic hepatitis, cirrhosis and liver cancer

28. Aspartate aminotransferase (ALT)
◦ ALT is more sensitive and specific for liver damage than AST
◦ Normal AST and ALT value are higher in men than women; also increases
with obesity.
• High serum levels in acute hepatitis (300-1000U/L)
• Moderate elevation in alcoholic hepatitis (100-300U/L)
• Minor elevation in cirrhosis, hepatitis C and non-alcoholic
steatohepatitis (NASH) (50-100U/L)

29. Aspartate aminotransferase (ALT)
◦ Appears in plasma many days before clinical signs appear
◦ A normal value does not always indicate absence of liver damage

30. ◦ Evaluation of abnormal liver function tests J K Limdi, G M Hyde, Postgrad Med J 2003;79:307–312

31. Alkaline phosphatase (ALP)
◦ A non-specific marker of liver disease
◦ Produced by bone osteoblasts (for bone calcification)
◦ Present on hepatocyte membrane
◦ Normal range: 30 – 120 U/L
◦ Non hepatic causes:
◦ Bone disease, chronic renal failure and lymphoma

32. Alkaline phosphatase (ALP)
◦ Moderate elevation observed in:
◦ Infective hepatitis, alcoholic hepatitis and hepatocellular carcinoma
◦ Very high levels of ALP (10–12 times of upper limit) may be noticed in
extrahepatic obstruction (obstructive jaundice) caused by gallstones or by
pressure on bile duct by carcinoma of head of pancreas.
◦ Drastically high levels of ALP (10–25 times of upper limit) are seen in bone
diseases where osteoblastic activity is enhanced. For example, Paget's disease
(osteitis deformans), rickets, osteomalacia, osteoblastoma, metastatic carcinoma
of bone and hyperparathyroidism.

33. ◦ Evaluation of abnormal liver function tests J K Limdi, G M Hyde, Postgrad Med J 2003;79:307–312

34. Gamma-glutamyltransferase (GGT)
◦ Used for glutathione synthesis
◦ Normal range: < 55 IU/L
◦ More specific for Biliary diseases than ALP
◦ Moderate elevation observed in:
◦ Infective hepatitis and prostate cancers
◦ GGT is increased in alcoholics despite normal liver function tests
◦ Highly sensitive to detecting alcohol abuse

35. ◦ Evaluation of abnormal liver function tests J K Limdi, G M Hyde, Postgrad Med J 2003;79:307–312

37. Common serum liver chemistry tests

38. LFT Interpretation

39. ENZYMES THAT REFLECT DAMAGE TO HEPATOCYTES
ALT : AST Ratio
•ALT > AST is associated with chronic liver disease
•AST > ALT is associated with cirrhosis and acute
alcoholic hepatitis

40. ENZYMES THAT REFLECT DAMAGE TO HEPATOCYTES
ALT : AST Ratio
◦ In most acute hepatocellular disorders, the ALT is higher than or equal to
the AST. (ALT > AST)
◦ Whereas the AST:ALT ratio is typically <1 in patients with chronic viral
hepatitis and nonalcoholic fatty liver disease.
◦ A number of groups have noted that as cirrhosis develops, this AST: ALT
ratio rises to >1. (AST>ALT)
◦ An AST:ALT ratio >2:1 is suggestive, whereas a ratio >3:1 is highly
suggestive, of alcoholic liver disease. (AST>ALT)

41. Enzymes that reflects cholestatic damage
ALP : GGT Ratio
◦ ALP with GGT = Cholestasis ( Impaired flow of bile from liver to
intestine)
◦ ALP with GGT normal = Bone pathology
◦ Sudden ALP & GGT = Hepatocellular Carcinoma
◦ Alcohol = GGT
◦ GGT is more specific for biliary disease.

42. ALT : ALP Ratio
•A greater than 10-fold increase in ALT and a less
than 3-fold increase in ALP suggests
a predominantly hepatocellular injury.
•A less than 10-fold increase in ALT and a more
than 3-fold increase in ALP suggests cholestasis.
•It is possible to have a mixed picture involving
both hepatocellular injury and cholestasis.

43. Liver test patterns in hepatobiliary disorders

44. ◦https://www.youtube.com/watch?v=i2PfjEks4
GQ&t=105s

45. AST to platelet ratio index (APRI)
◦ https://www.mdcalc.com/calc/3094/ast-platelet-ratio-index-
apri#evidence
◦ Liver biopsy is the recognized gold standard for liver fibrosis
staging. The aspartate aminotransferase to platelet ratio index
(APRI) has been proposed as a noninvasive and readily available
tool for the assessment of liver fibrosis in chronic hepatitis C
(CHC).

59. ◦MCQs

60. The best liver function is:
A. AST/ALT
B. Alkaline phosphate
C. Bilirubin
D.INR
d. INR
Of the above, only the IN is a true liver function test as it examines the capacity of the liver to synthesize
clotting factors. AST and ALT are enzymes that are elevated in hepatocellular injury. Alkaline phosphatase is
an enzyme that is elevated in cholestatic injury. Bilirubin is a pigment secreted by the liver that is elevated
with liver dysfunction but can also be elevated with bile obstruction (even though liver function is normal).

61. The two main patterns of liver injury are:
A. Hepatocellular and cholestatic
B. Cholestatic and Obstructive
C. Necrotic and hepatocellular
D.Neoplastic and cholestatic
Answer A
The two main patterns of liver injury are hepatocellular (main injury as the hepatocyte
level) and cholestatic (main injury at any level of the biliary excretory system). Liver
cell necrosis will lead to a nepalocellular injury pattern. obstruction or damage to the
bile ducts and infiltrauve disease will lead to cholestasis.

62. Clinical assessment
◦ A detailed history should
be taken and full physical
examination performed
with a particular emphasis
on alcohol consumption,
risk factors for viral
hepatitis..

66. Nurses role
Identify patient
Check physician orders
Suitable selection of supplies
Keep it Simple directions to client
Standard precautions
Label specimen
Timely Collect & Send to lab
Documentation

67. ◦ https://www.youtube.com/watch?v=lJreAmpHIzw

68. Case scenario
◦ A 54 year old patient consults with a six-month history of lethargy, but no other
significant red flag symptoms, and basic examination is unremarkable. At his
next visit, the only "significant" finding of a tiredness screen is a raised ALT of
84u/L and his remaining LFTs are normal.
◦ On review of his notes, he had LFTs checked two years ago which showed an
ALT of 65u/L but this was not acted on. At this time his BMI was 32. His
medical problems are noted to be pre-diabetes, osteoarthritis,
hypercholesterolaemia, obesity, atrial fibrillation and treated hypertension. His
medications consist of bisoprolol, simvastatin and lisinopril and PRN
naproxen. His CHAD2S2 VASc score is 1 and he has previously declined
anticoagulation.

69. Discussion
◦ In this case, the gentleman’s history reveals no significant risk factors and he
drinks around 4-6 units a week of alcohol with no evidence of dependence.
Examination reveals that he has a BMI of 38, his BP is 157/95 and there are no
stigmata of chronic liver disease.
◦ At this point you are likely to suspect non alcoholic fatty liver disease based on
the features of metabolic syndrome in this patient.
◦ After discussion, the patient undergoes a full liver screen including abdominal
ultrasound and returns for review. His AST is 65u/L with no other blood
abnormalities detected. Markers of synthetic liver function - platelet count,
clotting and albumin - are normal.
◦ Abdominal ultrasound scan reveals features consistent of fatty liver disease, with
no other significant abnormalities.

73. Take home message
• LFTs help detect liver injury and function.
• Abnormal LFTs tests may present in an asymptomatic patients.
• A good clinical history and physical examination are often rewarding.
• LFTs tests often become abnormal in non-hepatic diseases.

74. References
• Lippincott’s Illustrated Reviews Biochemistry: 6th edition, Unit IV,
Chapter 21, Pages 282 - 285.
• Lecture notes: Clinical Biochemistry: 9th edition, Chapter 13, Pages 174
- 187.
• Clinical Chemistry - Techniques, Principales and Correlations: 6th
edition, Chapter 24, Pages 520 -521.
• Roxe DM. Urinalysis. In: Walker HK, Hall WD, Hurst JW, editors. Clinical
Methods: The History, Physical, and Laboratory Examinations. 3rd
edition. Boston: Butterworths; 1990. Chapter 191.